Transcript CONTENT OF THE PRESENTATION 1. 2. 3. 4. Background Study Components and research findings I. Prevalence and Causative Factors for CKDu in Sri Lanka II.

CONTENT OF THE PRESENTATION
1.
2.
3.
4.
Background
Study Components and research findings
I.
Prevalence and Causative Factors for CKDu in
Sri Lanka
II. Socioeconomic and productivity impact of
CKDu
III. Nephrotoxic herbal remedies used in Sri Lanka
IV. Randomized Clinical trial to examine the renal
effects of an Angiotensin Converting enzyme
Inhibitor (Enalapril) in adults with CKDu
Recommendations
Future Studies
Background

Increase in a new form of CKD which is
NOT attributed to DM, HT, GN or other
Northern
known aetiologies observed

Case load more in certain areas i.e.
regional clustering

Insidious onset which probably starts in
second decade of life

Slowly progressive and asymptomatic
until very advanced

High economical cost for patient, family &
state
North Central
North Western
Eastern
Central
Uva
Western
Sabaragamuwa
Southern
Global Situation
Balka n Endem ic Nephropathy
CKD am ong se ver al sm a ll discr ete
com m uni tie s along the Da nube .
Andra Pr adesh, I ndia
High prev alence of C KD
in village s in Uddanam in
rem ote agr iculture be lt.
Nicar agua
CKDu am ong loca l
gr oup of e x-sugar
cane w or ker s.
El S alva dor
CKDu par ti cularl y
am ong younger m en
Source: Centre for Public integrity, Washington DC
INVOLVEMENT OF WHO -2008

Technical assistance
requested by Minister of
Health to WHO HQ


For review of available data
To initiate a coordinated,
multisectoral research effort
Add the letter
and a phon
picture of
JUSTIFICATION FOR A NATIONAL RESEARCH EFFORT….
Multiple Prevalence Rates!
Multiple Causative Agents!




Definition of CKDu to be
established and used as a standard
screening tool
Representativeness and nature of
populations screened unclear
Geographical mapping piece meal
Little coordination of
epidemiological, analytical &
environmental studies
ORGANISATIONAL STRUCTURE OF THE COLLABBORATIVE RESEARCH EFFORT
STRENGTHS OF THE STUDY
1.
Use of consistent case definition of CKDu
2.
Analysis of a range of biological samples from
CKDu subjects and controls
3.
Comparison of control groups within and
outside the endemic area
4.
Use of sensitive analytical techniques
5.
Heavy metals, metalloids and other elements
in environmental samples were analysed
ORGANISATIONAL STRUCTURE OF THE COLLABBORATIVE
RESEARCH EFFORT (Cont..)
MAIN SUB PROJECTS OF THE CKDu RESEARCH
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
II. Randomized Clinical trial to examine the
renal effects of an Angiotensin Converting
enzyme Inhibitor (Enalapril) in adults with
CKDu
III. Socioeconomic and productivity impact
of CKDu
IV. Nephrotoxic herbal remedies used in
Sri Lanka
MAIN SUB PROJECTS OF THE CKDu RESEARCH
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
II. Randomized Clinical trial to examine the
renal effects of an Angiotensin Converting
enzyme Inhibitor (Enalapril) in adults with
CKDu
III. Socioeconomic and productivity impact
of CKDu
IV. Nephrotoxic herbal remedies used in
Sri Lanka
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
Comprised of the following study components:
Ia
Population Prevalence Study
Ib
Analytical & Environmental Studies
Ic
Hospital Based CKD registry
Id
Geographical Mapping of identified variables
Ie
Establishment of a literature repository for CKD
Ia
Population Prevalence Study
Belaganwewa
Girandurukotte
Thissapura
Ambagaswewa
#
CD-SDMC Hebarawa
Thalakolawewa
DH-Girandurukotte
")
#
CD-Batalayaya
#
Hatharaskottuwa CD
Medirigiriya BH
#
G
F
#
Wijepura CD
3 Districts
#
Galamuna PU
!>
Jayanthipura RH
Pulasthigama RH
")
")
Aselapura CD
!C
Sevenapitiya CD
Mannampitiya PU
Attanakadawela RH
Parakrama Samudra CD
!>
DH-Uraniya
")
Welikanda RH
Polonnaruwa GH
RH-Ekkiriyankumbura
#
!>
!>
#
CD-Uva Tissapura
2
%
Singhapura CD
Diyabeduma CD
BH-Mahiyangana
#
Higurakgoda DH
CD-Dambana
#
G
F
Divulankadawala CD
DH-Kandeketiya
#
")
!>
DH-Meegahakiula
!>
RH-Roeberry
#
2
%
#
CD-Taldena
CD-Tennepanguwa
#
")
#
DH-Metigahatenna
PU-Galauda
2
%
!>
")
RH-Wewegama
!>
!>
RH-Kandegedara
PU-Badulla
2
!C%
GH-Badulla
Nuwaragala CD
Bakamuna PU
Aralaganwila PU
#
Ellewewa CD
2
%
#
")
Weheragala CD
Siripura CD
#
2
%
#
Daminna CD
#
#
#
#
CD Lunuwatta
DH-Uvaparanagama
!>
CD-Sylmiapura
")
#
!>
Padavi Parakramapura CD
!>
!>
RH-Ettampitiya
#
CD-Medagama
!>
!>
RH-Ury
RH-Hopton
RH-Springvelley
")
#
CD-Meedumpitiya
DH-Passara
DH-Welimada
#
RH-Nadungamuwa
!>
RH-Bogahakumbura
!>
DH-Lunugala
RH-Kahataruppa
RH-Kandagolla
CD-Haliela
CD-Keppetipola
#
CD-Hewankumbura
#
!>
6 Divisional
Secretariat
Areas
RH-Boralanda
G
F
!>
BH-Damodara
#
#
")
Padaviya DH PADAVIYA DH
")
G
F
CD-Halpe
RH-Mirahawatta
RH-Glananore
#
BH-Diyatalawa
")
CD-Namunukula
CD-Ballaketuwa
DH-Bandarawela
CD-Liyangahawela
DH-Haputale
Wahalkada PU
DH-Haldummulla
2
%
")
")
#
Thiththagonawa CD
!>
!>
Punawa RH
!>
DH-Koslanda
Kapugollagama RH
Kabathigollawa RH
Ethakada CD
#
Gonumeru Wewa
!>
Thanthirimale RH
")
!>
2
%
Madawachchiya DH
Rathmalgahawewa RH
^_
Gambirigaswewa GH
!>
^_
!>
Kendawa CD
#
Parasangaswewa RH Rambewa RH
!>
!>
Kallanchiya RH
# Wahagahapuwewa CD
")
Kahatagasdilliya DH
Ellayapaththuwa CD & MH
#
#
Puliyankulama CD
#
#
Mihinthale PU
Secred City CD
2
%
Mee - Kumbukwewa
Anuradapura GH
Prison Hospital
!C Pura CD
# Pubudu
# Wijepura CD
#
Galenbidunuwewa PU
2
%
Nelubawe RH
!>
Nochchiagama DH
#
2
%
Galkulama CD
!>
Nachchiyaduwa RH
!>
Thalawa PU
#
Koonwewa CD
Thammannawa RH
!>
Ranorawa RH
Devanumpiyathissapura CD
")
!C
Kokmaduwa
!>
Maha Willachchiya RH
Ellawewa
Pairamadu RH
Galadevulwewa CD
Huruluwewa GH
2
%
Rajanganaya-Track 11 GH
Gatalawa
Rajanganaya-Track 5 RH
!>
G
F
Thambuttegama BH
Hurulunikawewa Track 03 - 04
Eppawala PU
2
%
!>
#
Kattiyawa RH
!>
!>
Maradankadawala RH
Maha Illuppallama CD
Senapura RH
# Kunchikulam CD
Galnawa PU
!>
Negampaha RH
!>
Hurulumeegahapattiya
")
2
%
Kekirawa DH
!>
Habarana RH
Kalawewa RH
#
Galkiriyagama RH
!>
!>
22 Gramaniladhari
Divisions
Madawathugama CD
Adiyagala RH
2200 Households
(100 Houses from each GN)
Response
Rate
6,698 total eligible
6,132 responded to questionnaire
4,941 sampled (15-70 years)
74%
Ia
Population Prevalence Study (Cont..)
Methodology:
Participant Selection
6,698
Informed Consent
Detailed Questionnaire
6,132
Early Morning Urine Sample for
Urine ACR 4,941
Physical Examination
If ACR > 30mg/g
Capacity built of 50 Field volunteers
from the study areas
Repeat Urine ACR
HbA1C
Serum Creatinine
1,308
Ia
Population Prevalence Study (Cont..)
Case Definition for Chronic Kidney Disease of Uncertain
Aetiology (CKDu)
Urine ACR ≥ 30 mg/g on two occasions
 No past history of ureteric calculi,
glomerulonephritis, pyelonephritis or snake bite
 Not on treatment for diabetes
 Normal HbA1C (< 6.5%)
 If on treatment for raised Blood pressure BP <
140/90m if not on treatment for Blood pressure,
BP < 160/100

Ia
Population Prevalence Study (Cont..)
Grading of Chronic Kidney Disease of Uncertain Aetiology
(CKDu)
Grading Based on
eGFR
Grade 1
Grade 2
Grade 3
Grade 4
Persistent
Albuminurea and
eGFR
>90ml/min/1.73m2
Persistent
Albuminurea and
eGFR 60-89
ml/min/1.73m2
Persistent
Albuminurea and
eGFR 30-59
ml/min/1.73m2
Persistent
Albuminurea and
eGFR < 30
ml/min/1.73m2
PREVALANCE OF CKDu

Age standardized prevalence of CKDu was higher in
Females 16.9% (95%o CI = 15.5% to 18.3%) than Males 12.9%
(95%o CI = 11.5% to 14.4%)


Males
Females
Grade 1
27.0%
53.3%
Grade 2
27.9%
32.0%
Grade 3
23.2 %
7.4%
Grade 4
22.0 %
7.3%
Advanced grades (severe) of CKDu seen more among
males (p<0.001)
In both sexes the prevalence increased with increasing age
(p<0.001)
PREVALANCE OF CKDu

Why is there a difference in Male & Female
prevalence?

Low iron stores in females in lower socio economic groups
has influence on excretion of heavy metals and oxidative
stress on the kidney – making kidneys more vulnerable to
CKDu – resulting in higher prevalence in females

Male sex has been reported to be a risk factor for
progression to end-stage renal disease, and this may
partly explain the occurrence of more severe stages of
CKDu in men
PREVALANCE OF CKDu

Family history of kidney disease in parents or siblings in
20% individuals with CKDu

From individuals with CKDu





2.1% had ischaemic heart disease and/or cerebrovascular disease
0.4% had long term use of herbal medicine for hypertension
1.8% had a history of long term use of Aspirin
0.6% had a long term use of Analgesics
Being up Male reduced the risk of CKDu (OR=0.745, 95%
CI=0.562 to 0.988, P<0.05)

Being older than 39 years increased the risk of CKDu
(OR=1.926, 95% CI=1.561 to 2.376, P<0.001)
SUMMARY RESULTS OF LOGISTIC REGRESSION
ANALYSIS FOR EXPOSURE
Occupation Type – Being a chena cultivation
increased OR by 19.5%
Type of Agriculture – Engaging in paddy
cultivation compared to cultivation of
vegetables and other crops(chena cultivation)
decreased OR by 26.8%
Older Age, being female, being a farmer and being engaged
in non-paddy cultivation increased the odds of CKDu
DEMOGRAPHIC CHARACTESTICS OF CKDu
CASES
Characteristic
Non
Endemic
Area
Endemic Area
CKDu cases
Controls
Controls
Total Number
733
4044
250
Males, %
37.1
42.5
56
39.1 (14.2)
43.7 (13.9)
35.5 (14.0)
38
43.9
18.3
22.3 (4.6)
21.1 (4.1)
21.7 (4.4)
733
0
0
Age (years), mean (SD)
Farmer,%
BMI,kg/m2, mean (SD)
ACR > 30 mg/g
ACR Albumin-Creatinine ratio, BMI Body Mass Index, SD standard deviation
Ib

Analytical & Environmental Studies
This comprised of the following Components:
Ib
Analytical & Environmental Studies
Response Rate 74%
(n=4957)
ACR>30mg/g on two
occasions & other
criteria satisfied
(n=733)
Urine Arsenic,
Cadmium & Lead
Urine for other
elements
Serum Selenium,
Strontium etc
No diabetes, kidney
diseases, CKDu &
snake bite
(n=4044)
n=495
n=132
n=107
N=0
n=171
N=0
SPECIMEN HANDLING AND ANALYSIS





Samples were collected in uncontaminated collection vials and
stored frozen (−20°C) until transfer to the laboratory.
All analyses were performed in a contract laboratory
(Laboratory of Pathophysiology of the University of Antwerp,
Belgium), which has an external quality control scheme for
analysis of trace elements.
Measurements of Arsenic, Cadmium, Lead and other
elements in urine was performed by inductively coupled
plasma mass spectrometry (MS).
Serum analyses were performed by electrothermal atomic
absorption spectrometery.
Limits of detection for Aluminium, Strontium, Chromium and
Selenium were 0.1 μg/l, 0.5 μg/l, 0.01 μg/l and 1 μg/l
respectively.
RESULTS OF URINE – Arsenic, Cadmium & Lead
Arsenic
(ug/g creatinine)
Cadmium
(ug/g creatinine)
Lead
(ug/g creatinine)
CKDu
Cases
Controls
from
Endemic
Area
(EA)
Controls
Non
Endemic
Area
(NEA)
CKDu
Cases
Control
s from
Endemic
Area
(EA)
Controls
Non
Endemic
Area
(NEA)
CKDu
Cases
Control
s from
Endemi
c Area
(EA)
Controls
Non
Endemic
Area
(NEA)
n=495
n=132
n=250
n=495
n=132
n=250
n=495
n=132
n=250
45.447
92.443
56.572
1.039
0.646
0.345
1.153
1.254
2.099
Median
26.3
6.99
42.025
0.695
0.18
0.265
0.95
0.793
1.434
Range
0.4 616.6
0.2 966.29
5.38350.28
0.0058.93
0.0055.13
0.0052.079
0.048.53
1.216.64
0.27720.9
Mean
The sensitivity & specificity for concentrations of Cadmium in urine were 80% and 53.6% (AUC=0.682, 95% CI=0.61 to
0.75, cut off value > 0.23)
At a cut-off value of ≥0.397 μg/g, sensitivity was 70% and specificity 68.3%.
The sensitivity and specificity for the concentration of arsenic in urine were 90% and 23.2% respectively (AUC = 0.64, 95%
CI = 0.58 to 0.71, cut-off value ≥88.57 μg/g).
The concentration of lead in urine was a poor predictor of CKDu (AUC = 0.53, 95% CI 0.38 to 0.67)
RESULTS OF URINE
1
3
In Subjects with CKDu
urine Cadmium
excretion was significantly
higher compared to
control in both endemic
and non endemic areas
The sensitivity and
specificity for Urine
Cadmium were 80%
and 53.6%
respectively*
*AUC=0.682, cut off value >0.23µg/g
2
4
Controls in the endemic
area compared to those in
the non endemic area also
had significantly higher
urinary excretion of
Cadmium.
Dose-response analysis
showed that Cadmium
exposure is a risk factor
for the development of
CKDu* *
**P = 0.019 for stage 3 and P = 0.024 for
stage 4.
RESULTS OF URINE
6
5
The sensitivity and
specificity for
concentration of
Arsenic in urine was
90% and 23.2%
respectively*
The mean urine
concentration of Arsenic
in CKDu cases was above
levels known to cause
oxidative injury to
kidneys
7
There was no significant doseeffect relationship between
the concentration of Arsenic,
Lead or Selenium in Urine
and the stage of CKDu
*AUC = 0.64, 95% CI = 0.58 to 0.71, cutoff value ≥88.57 μg/g)
RESULTS OF URINE
8
Among CKDu cases, the
concentration of
Cadmium in Urine was
positively correlated with
Lead and Arsenic**
concentrations in urine
9
There was no
significant difference
in urine Arsenic and
Lead concentrations
in CKDu cases
compared to controls
**Lead (r=0.62, p<0.0001)
Arsenic (r=0.28, p<0.001)
RESULTS OF URINE – Other Metals
Metals mg/g creatinine
in CKDu subjects
n=107
Mean
Median
Minimum
Maximum
Sodium
Potassium
Calcium
Magnesium
Copper
Zinc
Titanium
4105.5
917.94
80.45
79.89
13.34
229.99
0.26
3544.00
800.00
67.00
80.00
11.00
235.99
0.24
425.00
243.00
4.00
2.00
3.70
31.00
0.03
17458.00
2469.00
368.00
169.00
91.10
510.00
0.88
Urine concentrations of sodium,
potassium, calcium, magnesium,
copper, zinc, and titanium in CKDu
cases were within normal limits
RESULTS OF SERUM
Concentration of metals in serum of subjects with CKDu
n= 171
Serum Concentration (µg/l)
Mean
Median
Minimum
Maximum
Aluminium
4.13
3.00
1.00
12.00
Chromium
0.118
0.06
0.01
1.15
Selenium
88.27
84.5
50.0
121.8
Strontium
83.17
82.00
29.00
198.00
Serum selenium reference range 54 -163 µg/l
Serum strontium reference range 14 - 84 µg/l
RESULTS OF SERUM
2
1
Serum
Aluminium and
Chromium levels
were within normal
levels
3
Serum Strontium
levels were above
normal limits**
About two-thirds
(63%) of CKDu
subjects had
Selenium levels
below 90μg/l.*
*Serum Selenium levels in CKDu subjects ranged
from 50.0 μg/l to 121.8 μg/l(reference range = 54 μg/l
to 163 μg/l).
A serum selenium concentration of 90 μg/l is required
to reach the maximum level of glutathione peroxidise
The sensitivity and specificity for serum selenium
were 80% and 60% respectively (AUC = 0.789, cut =
off value ≥94.3 μg/l
** Serum strontium levels were above
normal limits (mean = 83.17 μg/l,
standard deviation [SD] = 32.15 μg/l;
reference range = 14 μg/l to 84 μg/l).
RESULTS OF NAILS & HAIR
Source
Nail – CKDu
cases
(n=80)
Nail - Control
(n=48)
1 A significantly higher
Cadmium
concentration was
seen in the nails of
CKDu cases*
*( P < 0.05).
Mean
Median
Minimum
Maximum
Mean
Median
Minimum
Maximum
2
Nails
Hair
Cadmium
(ug/g)
0.017
0.007
0.001
0.347
0.009
0.001
0.001
0.091
Arsenic (ug/g)
0.144
0.139
0.000
0.452
0.125
0.103
0.006
1.214
Arsenic levels in hair
were significantly
higher in CKDu
Cases**
**( P < 0.05).
KEY MESSAGES





CADMIUM
Cadmium is a known nephrotoxin
Urinary Excretion of Cadmium is a reliable indicator of
cumulative long-term exposure to cadmium
The mean urine concentration of cadmium in CKDu
cases was above the levels demonstrated in recent
studies to cause oxidative stress and decreased
glomerular filtration rate and creatinine clearance
A significantly higher cadmium concentration was also
seen in the nails of those with CKDu compared to
controls from the endemic area.
The results of this study indicate that cadmium exposure
is a risk factor for CKDu.
KEY MESSAGES




ARSENIC
The mean urine concentration of arsenic in CKDu
cases was also above levels known to cause oxidative
injury to the kidney
In CKDu cases and controls from the endemic area,
concentrations of arsenic in urine and in fingernails were
higher than those reported in people living in lowexposure environments.
Urine is a major pathway for excretion of arsenic from
the human body and so urine levels reflect exposure.
In some studies, markers of oxidative stress have been
demonstrated at urine arsenic concentrations as low as
3.95 μg/g
KEY MESSAGES


ARSENIC
The level of total arsenic in urine is associated with
chronic kidney disease in a dose–response relationship,
especially when the level is greater than 20.74 μg/g.
Co-exposure to cadmium and arsenic is known to
produce additive effects on the kidney that are more
pronounced than exposure to either metal alone
KEY MESSAGES




SELENIUM
Selenium has been shown to protect the kidney from
oxidative stress
A selenium concentration of 80–95 μg/l is needed to
maximise the activity of the antioxidant enzyme
glutathione peroxidase and selenoproteins in plasma
Serum Selenium was below 80 μg/l in 38% and below
90 μg/l in 63% of individuals with CKDu.
Low selenium levels may have been a contributory factor
increasing the vulnerability of the kidneys to oxidative
damage caused by heavy metals and metalloids.
KEY MESSAGES
STRONTIUM
The association of raised Serum strontium levels with
 raised serum cadmium levels has been reported
previously
 Strontium levels were not analysed in food or water.
 The most likely explanation is an alteration of
Strontium handling and excretion, owing to the effect of
Cadmium on renal tubular function.

Ib

Analytical & Environmental Studies
Details of Environmental Samples Collected for cross
Sectional Comparison:
Water
Fertillisers
Weedicides
& Pesticides
Food
Environmental
Samples
Soil
Weeds
Tobacco,
Beetle &
Beedi
SPECIMEN HANDLING AND ANALYSIS



Samples were collected in uncontaminated collection vials and
stored frozen (−20°C) until transfer to the laboratory.
All analyses were performed in a contract laboratory
(Laboratory of Pathophysiology of the University of Antwerp,
Belgium), which has an external quality control scheme for
analysis of trace elements.
Measurements of Arsenic, Cadmium, Lead and other
elements in water, vegetables, agrochemicals and soil, was
performed by inductively coupled plasma mass spectrometry
(MS).
RESULTS OF WATER ANALYSIS
99
123
12
• Sources of drinking water for individuals with CKDu in
Endemic Area
• (from ground well, tube wells and natural springs)
• Other sources of water from Endemic Area
• (From ground wells, tube wells, irrigation canals
• Non Endemic Area
RESULTS OF WATER ANALYSIS
Arsenic
Lead
Cadmium
Uranium
End canal = endemic area canal; End drink = endemic area drinking water; End reser = endemic area reservoir; End spring =
endemic area spring;nonend drink = non-endemic area drinking water. Horizontal lines within the boxes represent the median
values. The ends of the solid lines extending on either side of the boxes represent the minimum and the maximum. The dark
dots are outliers; defined as being more than 1.5 interquartile ranges away from the box. The interquartile range is the distance
between the upper part of the box and the lower part of the box.
RESULTS OF WATER ANALYSIS
2
1
Levels of Cadmium, Lead
and Uranium in sources
of drinking water used by
individuals with CKDu
were within normal
limits.
Arsenic was borderline or
raised in four samples* of
drinking water used by
individuals with CKDu
repeat analysis from the
four sources showed
normal Arsenic levels.
Reference limits: Arsenic <10 μg /l, Cadmium <3 μg/l, Lead <10 μg/l, Uranium <2 μg/l
*(9.9 μg/l, 10.2 μg/l, 10.5 μg/l,13.4 μg/l).
RESULTS OF WATER ANALYSIS
4
3
In water samples from other
sources in Endemic area, the
Arsenic concentration was
22.2 μg/l and 9.8 μg/l in two
samples taken from a canal
and a reservoir,
The Cadmium
concentration was 3.46 μg/l in
one sample from a reservoir
The Lead concentration was
12.3 μg/l in one sample from a
reservoir in the endemic area.
All other samples from
wells, tube wells, irrigation
canals, pipe-borne water,
reservoirs and natural
springs from endemic and
non-endemic area, had
normal Arsenic,
Cadmium and Lead
levels.
Reference limits: Arsenic <10 μg /l, Cadmium <3 μg/l, Lead <10 μg/l, Uranium <2 μg/l
KEY MESSAGES




DINKING
WATER
The Cadmium content in all water samples analysed
was within normal limits, except in one sample from a
reservoir that had a borderline cadmium level (3.45 μg/l).
Drinking water is a major pathway for entry of inorganic
Arsenic into the human body.
The arsenic content in 99% of water samples was below
the WHO reference value of 10 μg/l.
However, it has recently been suggested that the
concentration of arsenic in drinking water should be no
more than 5 μg/l.
KEY MESSAGES




DINKING
WATER
CKDu occurs in areas where groundwater is the main
source of drinking water. Groundwater in this region is
known to have a high content of Fluoride and Calcium.
People living in the region for generations have used
groundwater for drinking without ill effects.
However –



hardness of water, the high fluoride content,
Poor access to drinking water
Inadequate intake of water in a warm climate
may influence the body burden and/or the excretion of
heavy metals and oxidative damage to the kidneys caused
by heavy metals.
RESULTS OF FOOD ANALYSIS
119
• Rice, Pulses,Vegetables including leafy vegetables, Coconut,
Yams & roots (eg: Kohila, Lotus), Fresh Water fish, Tobacco,
Pasture & Weeds from Endemic area
32
• Rice, Pulses,Vegetables including leafy vegetables, Coconut,
Yams & roots (eg: Kohila, Lotus), Fresh Water fish, Tobacco,
Pasture & Weeds from Non Endemic area
RESULTS OF FOOD ANALYSIS
Arsenic
Lead
Cadmium
Horizontal lines within the boxes represent the median
values. The ends of the solid lines extending on either
side of the boxes represent the minimum and the
maximum. The dark dots are outliers ; defined as being
more than 1.5 interquartile ranges away from the box.
The maximum levels of cadmium permitted by the Codex
Alimentarius for vegetables is 0.2 mg/kg and by the
Commission of the European Communities is 0.05 mg/kg
[The maximum concentration of cadmium stipulated for
certain types of fish by the Commission of the European
Communities is 0.05 mg/kg.
The maximum concentration of lead stipulated for
vegetables by the Commission of the European
communities is 0.10 mg/kg .
RESULTS OF FOOD ANALYSIS
Levels of Cadmium in
Rice in both Endemic &
Non Endemic areas were
below the allowable limit
(0.2mg/kg)
Levels of Cadmium in
certain vegetables such as lotus
root, and in tobacco, were high.
Levels of Cadmium in lotus
and tobacco were higher in
endemic than in non-endemic
areas
The maximum concentration
of Cadmium in vegetables in
the endemic area was 0.322
mg/kg and in the non endemic
areas it was 0.063 mg/kg
Source
Lotus
Mean
Median
Maximum
Tobacco Mean
Median
Maximum
Cadmium (mg/kg)
Endemic Area Non Endemic
(EA)
Area (NEA)
0.413
0.066
1.50
0.351
0.351
0.44
0.023
0.023
0.03
0.316
0.316
0.351
KEY MESSAGES


FOOD
TOBACCO
The maximum level of Cadmium for vegetables permitted
by the Codex Alimentarius is 0.2 mg/kg
The level of Cadmium & Lead permitted by the Commission
of the European Communities
Cadmium - 0.05 mg/kg.
Lead -0.10mg/kg

The maximum levels in certain vegetables grown in the
endemic area exceeded these safety levels.
Fish -Cadmium (0.06 μg/g)*
Vegetables in the endemic area - Lead (0.476 mg/kg)
Levels of cadmium and Lead in vegetables and Cadmium
in freshwater fish from the endemic area are above
the maximum levels stipulated by certain Food SafetyAuthorities

also exceeded the European maximum
limit of 0.05 mg/kg stipulated for certain types of fish
FOOD
TOBACCO
KEY MESSAGES

A provisional tolerable weekly intake (PTWI) established by
the Joint Food and Agriculture Organisation of UN (FAO) /
WHO Expert committee on Food Additives ( JECFA) for body
weight per week


Cadmium- 5.8(ug/g)
Arsenic - 0.015(mg/kg)

Lead
2.52(ug/g)*
Level withdrawn – To keep low
as possible
- 0.025(mg/kg)
Since the Cadmium content of certain food items in the endemic area
is above stipulated levels, the total weekly intake of cadmium in
people living in the endemic area could exceed these safe limits, with
detrimental effects on the kidneys, particularly in vulnerable people
and those with predisposing factors.
RESULTS OF SOIL ANALYSIS
88
41
• Soil samples were obtained from paddy fields, other
types of cultivations and reservoirs from Endemic
area
• Soil samples were obtained from paddy fields and
other types of cultivations from Non Endemic
area
RESULTS OF SOIL ANALYSIS
Source
Paddy
Mean
EA(n=45)
Median
NEA (n=21) Minimum
Maximum
Chena
Mean
EA(n=20)
Median
NEA (n=10) Minimum
Maximum
Vegetable Plot Mean
EA(n=23)
Median
NEA (n=10) Minimum
Maximum
Crop land
Mean
EA (n=6)
Median
NEA (n=2)
Minimum
Maximum
Reservoir
Mean
EA (n=6)
Median
NEA (n=3)
Minimum
Maximum
Arsenic (ug/g)
Endemic
Non
Area (EA)
Endemic
Area (NEA)
0.16
0.17
0.11
0.08
0.00
0.01
0.85
0.99
0.06
0.40
0.04
0.29
0.00
0.09
0.22
1.57
0.11
0.27
0.07
0.24
0.00
0.08
0.46
0.53
0.05
0.13
0.06
0.13
0.00
0.09
0.01
0.18
0.60
0.50
0.17
0.43
Cadmium (ug/g)
Lead (ug/g)
Endemic Non Endemic Endemic Area
Non
Area (EA) Area (NEA)
(EA)
Endemic
Area (NEA)
0.49
0.45
16.54
14.49
0.43
0.40
15.75
16.95
0.16
0.01
5.03
0.02
0.56
1.61
34.54
39.95
0.40
0.59
15.41
14.84
0.36
0.55
13.82
13.93
0.17
0.34
8.25
5.42
1.27
0.93
28.33
26.1
3.48
0.47
17.46
18.01
0.37
0.41
16.76
18.03
0.16
0.29
6.69
5.57
70.00
0.84
41.02
32.87
0.60
0.28
20.55
7.96
0.5
0.28
20.29
7.96
0.17
0.24
9.98
3.15
1.47
0.33
32.1
12.77
0.66
19.16
0.52
17.16
0.15
7.11
1.36
33.49
RESULTS OF SOIL ANALYSIS
The mean Cd
Concentration of soil
from the endemic
area was 0.4µg/g.
The level of Cadmium in
surface soil in the endemic
area (n = 94, excluding
samples from reservoirs), was
1.16 μg/g compared to 0.49
μg/g in the non-endemic area
(n = 45,excluding samples from
reservoirs)
KEY MESSAGES



SOIL
The mean concentration of Cadmium in soil from the
endemic area was 0.4 μg/g.
Surveys of agricultural soils in the USA and Sweden have
reported lower soil cadmium levels (0.265 mg/kg and 0.23
mg/kg respectively)
The concentration of Cadmium, Arsenic and Lead
in soil, and their impact on body burden and excretion,
is known to be influenced by many environmental factors:




pH of soil
Buffering capacity
Content of organic matter
Water quality
KEY MESSAGES



SOIL
Cadmium accumulation by plants, for example, is
influenced by the reactive soil cadmium content and pH.
It is decreased by high cation exchange capacity of
the soil and increased by higher soil temperature
The hardness and high content of fluoride in water in the
endemic area may also influence the dynamics of cadmium in
soil, absorption by plants and excretion from the kidney.
RESULTS OF WEEDICIDES & PESTICIDES
Arsenic (ug/g)
Endemic Area
(EA)
n=26
Mean
Median
Minimum
Maximum
6.73
1.68
0.01
94.93
Cadmium (ug/g)
Lead (ug/g)
Non Endemic Endemic Area Non Endemic Endemic Area Non Endemic
Area (NEA)
(EA)
Area (NEA)
(EA)
Area (NEA)
n=8
n=26
n=8
n=26
n=8
3.81
1.38
0.01
13.15
0.77
0.31
0.05
9.34
0.76
0.3
0.05
2.0
40.62
1.79
0.83
930.81
15.65
1.89
1.01
56.39
A total of 26
samples analyzed
from endemic
areas
RESULTS OF PHOSPHATE FERTILIZERS
Cadmium (ug/g)
Lead (ug/g)
Arsenic (ug/g)
Endemic Area Non Endemic Endemic Area Non Endemic Endemic Area Non Endemic
(EA)
Area (NEA)
(EA)
Area (NEA)
(EA)
Area (NEA)
n=13
n=6
n=13
n=6
n=13
n=6
Mean
Median
Minimum
Maximum
2.98
0.04
0.01
30.79
0.49
0.03
0.01
1.28
94.23
1.42
0.17
823.41
The maximum acceptable
levels for Cadmium, Lead and
Arsenic, in phosphate
fertilizer product, at 1% of the nutrient
level, are 4 μg/g, 20 μg/g and 2 μg/g,
respectively
20.29
0.65
0.09
98.52
0.06
0.04
0.00
0.19
A total of 19 samples
analyzed
(TSP – 6, MOP – 3,
Urea – 7, Mixed - 3)
0.43
0.19
0.00
1.22
Ib
Analytical & Environmental Studies
SPECIMEN HANDLING AND ANALYSIS

Samples were shipped in dry ice and stored at −18°C until
analysis. Analysis used validated liquid chromatography
with tandem MS (LC-MS/MS), gas chromatography-mass
spectroscopy (GC-MS) and gas chromatography with tandem
mass spectrometry (GC-MS/MS) methods
RESULTS OF PESTICIDE RESIDUES
Parent Compound
Bio Marker
Reference
Range
(μg/l)
CKDu cases
(μg/l)
(Minimum,
Maximum)
CKDu cases
above reference
limit (%)
<0.3
0.5,0.62
3.5
<2
0.3,2.2
1.7
<11.3
0.5,34.7
10.5
<25
0.5,8.88
0
2,4-D
2,4-D
Pentachlorophenol
Petachlorophenol
Chlorpyrifos
3,5,6-trchloropyridinol
Parathion
P-nitrophenol
Carbaryl
Naphthalene
1-naphthol
<19.7
0.5,45.1
10.5
Naphthalene
2-naphthol
<17.1
0.5,47.88
10.5
Glyphosate
Glyphosate
<2
0.075, 3.36
3.5
Glyphosate
AMPA
<0.5
0.075, 2.65
14
RESULTS OF PESTICIDE RESIDUES
Pesticide residues
were detected in the
urine from individuals
with CKDu
Pesticide Residue
Frequency of
detection
2,4-D
33%
3,5,6-trichloropyridinol
70%
P-nitrophenol
58%
1-naphthol
100%
2-naphthol
100%
Glyphosate
65%
Aminomethyl phosphonic acid (AMPA)
28%
Ib
Analytical & Environmental Studies
Postmortem tissues (kidney cortex,
liver & bone) of 40-60 years
 26 CKDu patients
 16 accident victims
Analyzed for Arsenic, Cadmium &
Lead
RESULTS OF POST MORTEM TISSUE
Kidney
Liver
Bone



Mean
Median
Minimum
Maximum
Mean
Median
Minimum
Maximum
Mean
Median
Minimum
Maximum
Arsenic
(ug/g)
885.54
152.62
19.28
7458.54
165.39
117.19
22.22
1471.41
8.68
4.87
0.82
70.66
Cadmium
(ug/g)
4.04
2.34
0.0384
14.16
5.38
2.42
0.13
26.16
6.47
4.34
0.47
28.84
Lead
(ug/g)
0.89
0.6
0.01
2.54
4.56
3.93
0.98
13.33
64.04
47.13
2.11
233.92
Cadmium & Lead contents in bone tissues of known CKDu
patients were higher than that for controls
No significant difference in levels of Arsenic in bones of
cases & controls
No significant difference in levels of all 3 metals in kidney
cortex & liver tissues of cases & controls
Ib
Analytical & Environmental Studies
Completed….
Ic
Hospital Based CKD registry
Main objectives:

To characterize CKD / CKDu population
attending renal clinics in :
Medawachchiya DH
Medirigiriya BH
Anuradhapura GH
Polonnaruwa GH

Database created with following:

Basic socio-demographics

Lifestyle

Environmental factors,

Anthropometry

Results of lab investigations
RESULTS OF HOSPITAL BASED CKD REGISTRY
Medawachchiya DH
13%
Medirigiriya BH
25%
Polonnaruwa GH
14%
Female
28%
Anuradhapura GH
48%
Cases Registered in the hospital registry - 1997
True CKDu cases
- 775 (39%)
Conversion to a National Registry
Male
72%
Id
Geographical Mapping of identified variables
Household
Maps
2200 Households
Sample
Survey Maps
mapped upto GN level
Water
Fertillisers
Weedicides
&
Pesticides
Food
Environmental
Samples
Soil
Approximately 450
sampling sites mapped
Capacity of 50 field volunteers built from the area
Weeds
Tobacco,
Beetle &
Beedi
IeId
Establishment of a literature repository for CKD
Collection & Collation of CKDu literature from 1998 - 2003
Literature collected under the following:
Global
Perspective
Risk Factors
Presentations
WHO CKD
study notes
General
Epidemiological
Heavy Metals
Biochemistry
Histology
Miscellaneous
Other related
literature
(International
Publications
Geographical
Water analysis
Flouride
Toxins
Trace elements
Radionuclides
MAIN SUB PROJECTS OF THE CKDu RESEARCH
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
II. Randomized Clinical trial to examine the
renal effects of an Angiotensin Converting
Enzyme Inhibitor (Enalapril) in adults with
CKDu
III. Socioeconomic and productivity impact
of CKDu
IV. Nephrotoxic herbal remedies used in
Sri Lanka
II. Randomized Clinical trial to examine the renal
effects of an Angiotensin Converting enzyme Inhibitor
(Enalapril) in adults with CKDu
To examine renal effects of Enalapril versus placebo in adults
with CKDu by comparing and evaluating the effect of Enalapril
to placebo on:
•Estimated GFR
•Albuminuria
•Change in stage of CKDu
•Randomized, double blind, placebo controlled clinical trial
•Study settings are special clinics organised in
•Anuradhapura TH
Analysis of Results
•Padaviya BH
Awaited
•Medirigiriya BH
•A total of 266 participants recruited and randomized
RESULTS OF RANDOMISED CLINICAL TRIAL
Levels of Cadmium in
Rice in both Endemic &
Non Endemic areas were
below the allowable limit
(0.2mg/kg)
Levels of Cadmium in
certain vegetables such as lotus
root, and in tobacco, were high.
Levels of Cadmium in lotus
and tobacco were higher in
endemic than in non-endemic
areas
The maximum concentration
of Cadmium in vegetables in
the endemic area was 0.322
mg/kg and in the non endemic
areas it was 0.063 mg/kg
Source
Lotus
Mean
Median
Maximum
Tobacco Mean
Median
Maximum
Cadmium (mg/kg)
Endemic Area Non Endemic
(EA)
Area (NEA)
0.413
0.066
1.50
0.351
0.351
0.44
0.023
0.023
0.03
0.316
0.316
0.351
MAIN SUB PROJECTS OF THE CKDu RESEARCH
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
II. Randomized Clinical trial to examine the
renal effects of an Angiotensin Converting
enzyme Inhibitor (Enalapril) in adults with
CKDu
III. Socioeconomic and productivity impact
of CKDu
IV. Nephrotoxic herbal remedies used in
Sri Lanka
III. Socioeconomic and productivity impact of CKDu

Consisted of two research components:
•To estimate costs of CKDu to individual, household &
communities
•To understand psychosocial impact
•Describe modes of coping at all levels
•Evaluate impact of existing coping mechanisms
IIIa
Community Based Study
IIIb
Hospital Based Study
•To estimate the socioeconomic impacts of CKDu & to
identify methods of easing burden
IIIa
Community Based Study
Study area: Padaviya & Madawachchiya DS Divisions
200
questionnaires
& in depth
interviews
16
Key
informant
Interviews
22
Case studies
(with regard
to death of
CKDu
person)
23
Focus Group
discussions
RESULTS OF COMMUNITY BASED STUDY
Community
Discourse
• Fear with regard to the illness, and social & emotional
cost due to stigma
Treatment
seeking
behavior
• Majority go to clinic (public sector) regularly.
• No demand for indigenous medical system & private
sector services.
• A greater demand for religious/ritual healing practices
Psychosocial
Impact
• Social & emotional dimensions of patients/ families
neglected by healthcare delivery system
• (attributed to clinical limitations & communication gaps)
RESULTS OF COMMUNITY BASED STUDY
(Cont…)
Impact on
Everyday life
• Affect livelihood activities, domestic tasks & social activities.
• Struggle to continue with normal lifestyle.
• For some exceptional cases, life has become further active after
diagnosis where patients expedited certain tasks to fulfill family
& social responsibilities GILGI
Impact on
family &
community
• Drastic changes within the family in the domains of resource
allocation, consumption patterns, setting priorities & social
relationships.
• Entire community affected due to deteriorating both valuable
human resources & material resources
Coping
mechanism
• Perceive illness as incurable & death is inevitable, & adopt various
strategies to cope with the situation.
• Such strategies often push patients/ families into more poverty &
extreme vulnerability.
• Lack of institutionalized social support systems further aggravate
the situation
CKDu should be looked as not merely a medical issue but as
a social issue
IIIb
Hospital Based Study
Hospital Based costing studies
• To determine costs of CKDu to
the health system and individual
• Studies done in:
• Padaviya DH
• Madawachiya DH
• Anuradhapura TH
• Renal Care & Renal Research
Centre Anuradhapura
• Following analysed:
• Average duration of hospital
stay
• Medical Costs for each clinic
visit
• Average cost per outpatient
visit
Economic Analysis
• For economic analysis and
estimation of income and output
loss
• Costs to households of
treatment & care
• Cost to household of hospital
stay
• Hospital costs for clinic and
inpatient care
• Indirect costs from low
productivity, absence from work
and premature death
Data Collection
through
questionnaires
RESULTS OF HOSPITAL BASED STUDY – COST
TO PATIENTS
Total No of clinic patients – 305
Key demographic features of the clinic
patients were:
Clinic
patients
74% Males
Mean age 56years
98% Sinhalese
98% Buddhists
50% were skilled agriculture and fishery workers
whilst 40% were unemployed
54% monthly family income was Rs5000-20000
RESULTS OF HOSPITAL BASED STUDY- COST TO
PATIENTS
Cost Median (LKR)
74% used the bus to attend clinic
1000
900
800
700
600
500
400
300
200
100
0
Clinic
patients
Direct cost of the last clinic visit of the participant Direct
Costs
Cost Item
RESULTS OF HOSPITAL BASED STUDY-COST TO
PATIENTS
Median time spent on the clinic visit by a participant was 8
hours
Indirect Cost of patients seeking clinical care
Clinic
patients
Indirect
Costs
1200
1000
800
600
400
200
0
Lost income by patients (n=11)
Payment for covering work (n=43)
Lost income by family members (n=35)
RESULTS OF HOSPITAL BASED STUDY-COST TO
PATIENTS
Inpatients
(Including those
Total No of inpatients – 132
on dialysis)
Mean duration of hospitalisation – 1 day
Key demographic features of the hospitalised patients were:
71% Males
Mean age 49 years
93% Sinhalese
92% Buddhists
39% were skilled agriculture and fishery workers
whilst 63% were unemployed
54% monthly family income was Rs5000-20000
RESULTS OF HOSPITAL BASED STUDY – COST
TO PATIENTS
Inpatients
56% used a hired three wheeler to reach
(Including those
on dialysis)
hospital
Median Cost (LKR)
Direct cost of the hospitalisation
1000
900
800
700
600
500
400
300
200
100
0
Cost Item
Direct
Costs
RESULTS OF HOSPITAL BASED STUDY – COST
TO PATIENTS
Inpatients
Indirect cost of the hospitalisation
Cost median (LKR)
1200
(Including those
on dialysis)
Indirect
Costs
1000
800
600
400
200
0
Lost income by
patient (n=3)
Payment for covering
work (n=7)
Cost Item
Lost income by
family members
(n=29)
RESULTS OF HOSPITAL BASED STUDY – COST
TO HEALTH SYSTEM
Overheads
Utilities
Based on clinic services at Anuradhapura Renal Unit
Telecommunication
Electricity
Fuel
13,607
24,079
Security Services
13,844
Laundry Services
11,809
Cleaning Services
Paramedical
Average Number of
patients attending renal
clinic per month 1763
68,940
15,152
Support
Personnel
1,046
Water
Meals
Unit cost of clinic
care Rs 866.74 per
patient visit
32,050
130,705
58,747
Nursing
Medical
Cost of
clinic care
897,913
260,178
RESULTS OF HOSPITAL BASED STUDY – COST
TO HEALTH SYSTEM
Inpatient
care
Based on Renal Unit at Anuradhapura TH
Utilities
Telecommunication
10,024.47
Electricity
660,886.30
Water
145253.08
Fuel
130446.34
Overheads
Meals
230830.84
Securtity services
132711.12
Laundry Services
113205.47
Cleaning Service
307241.55
Support
Personnel
Average Number of
patients hospitalized per
month is 1182
406524.48
Paramedical
88119.9
Unit cost of
hospitalization per
patient per day is
Rs 3351.32
Nursing
1346870.09
Medical
390,266.75
0.00
200,000.00 400,000.00 600,000.00 800,000.00 1,000,000.001,200,000.001,400,000.001,600,000.00
Detailed cost per month (LKR)
RESULTS OF HOSPITAL BASED STUDY – COST
TO HEALTH SYSTEM
Based on haemodialysis in the high dependency unit of
Anuradhapura TH
Cost of Haemodialysis
Drugs
Rs 607.47
Cost of haemodialysis
was estimated in a
sample of 58 patients
Total Cost per
patient per dialysis
session is
Rs 7,183.13
Haemodiaysis
Rs 4,900
Dialysis
Care
Hospitalization
Rs 1,675.66
RESULTS OF HOSPITAL BASED STUDY – COST
TO ILLNESS TO COMMUNITY
A sample of 200 patients chosen from Padaviya and
Madawachchiya
Three issues identified from cost of
care perspective
Travel cost
(Regular clinic
care needed
sometimes in
more than one
location)
The need for
Multiple Clinic
Visits
“Care when
needed”-which
results in
patients seeking
off hospital &
private sector
treatment
III. Socioeconomic and productivity impact of CKDu
Recommendations
Social
Welfare
system
Transport
Health
system
Patient
Allowance
• To be provided at household level
• Better modes of transport to hospitals and clinics
•
•
•
•
Long waiting times to be reduced
Reduce the need for household purchase of drugs
Reduce need for private sector investigation
More provision for haemodialysis
• To be provided at an earlier stage of the illness
MAIN SUB PROJECTS OF THE CKDu RESEARCH
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
II. Randomized Clinical trial to examine the
renal effects of an Angiotensin Converting
enzyme Inhibitor (Enalapril) in adults with
CKDu
III. Socioeconomic and productivity impact
of CKDu
IV. Nephrotoxic herbal remedies used in
Sri Lanka
IV. Nephrotoxic herbal remedies used in Sri Lanka

Herbal / Ayurvedhic medicines containing Aristolochic
Acid implicated as a causative factor for Renal Disease
Objectives of the study
To examine the species of
Aristocholia that grow in Sri
Lanka particularly in CKDu
high prevalent areas
To list the species that are
ingredients of traditional
/herbal remedies
particularly used in CKDu
high prevalent areas
RESULTS OF NEPHROTOXIC HERBAL REMEDY
STUDY
Distribution of Aristolochoia Species
in Sri Lanka
Other Species found in Sri Lanka:
•Aristalochia labiosa
•Aristalochia littoralis
•Aristalochia bracteolata
RESULTS OF NEPHROTOXIC HERBAL REMEDY
STUDY
Usage of of Aristolochoia Species
In Sri Lanka about 66 Ayurvedic
prescriptions contain Aristlochia
(Sapsanda/Sasanda) for treatment
of more than 20 diseases
MAIN SUB PROJECTS OF THE CKDu RESEARCH - RECAP
I. Prevalence and Causative Factors for
CKDu in Sri Lanka
II. Randomized Clinical trial to examine the
renal effects of an Angiotensin Converting
enzyme Inhibitor (Enalapril) in adults with
CKDu
III. Socioeconomic and productivity impact
of CKDu
IV. Nephrotoxic herbal remedies used in
Sri Lanka
CONCLUSION
1.
2.
3.
4.
5.
Results of the study indicates that 15% of the people in the North Central
Region are affected by CKDu
Results of this cross sectional study do not indicate that a single agent is
responsible for the pathogenesis of CKDu
Based on data reported, this study concludes a triple threat to the kidneys:
 Low levels of Cd through the food chain
 Coupled with deficiency of Selennium
 Concurrent exposure to As and pesticides
Water does not appear to be the source of exposure – However
improving water quality and supply will possibly reduce the body burden of
heavy metals as well as possible role of Fluoride, Hardness, Ca, Na.
CKDu is causing catastrophic expenditure to the state and the affected
individuals and this is leading to a new kind of poverty and stigma in the
community
RESPONSE FROM GOVERNMENT OF SRI LANKA
TO RESEARCH FINDINGS
October 2012 - Inter-ministerial committee appointed to
review indiscriminate use of chemical fertillisers and
agrochemicals
October 2012 – Inter-ministrial Officials Committee appointed
for CKDu (Ministry Secretaries)
October 2012 – x4 Subcommittees appointed by the
ministerial /officials committee
November 2012 - Parliamentary Advisory Committee on
Agriculture
March 2013 – Ministry of Health Cabinet Paper presenting the
recommendations of the WHO final report
May 2013 –Ministry of Agriculture Cabinet paper presenting 15
recommendations
May 2013 – Minister (Senior) for Rural Affairs & Chairman of the
Committee to look into Indiscriminate use of fertilizer & Agrochemicals
INDISCRIMINATE USAGE IF CHEMICAL FERTILIZER AND
AGROCHEMICALS
The Ministerial
committee
The Officials
Committee
Fertlliser use in Sri
Lanka with Special
reference to CKDu
Pesticides (Including
Weedicides,
herbicides and
fungicides) used in
Sri Lanka with
special reference to
CKDu
1st Meeting on
November
2012
Organic Agriculture
in Sri Lanka
Research findings on
the effect of soil
agriculture, water,
fertiliser and
pesticide use on
CKDu & any other
links such as food &
drinking water
Ministry of Health - Cabinet Memorandum
1
Water purification schemes to be scaled up
2
Strengthen the regulatory framework to improve quality control of imported
agrochemicals
3
Implement and monitor comprehensive public health measures to reduce the
exposure of farmers to harmful health effects of agrochemicals
4 Improve service provision for early detection of CKDu, hypertension and
diabetes and appropriate treamtment
5
Increase the financial assistance provided to farmer families affected by CKDu
6 Increase awareness among among Ayurvedic practitioners of the nephrotoxic
effects of Aristolochia Indica (sapsanda)
7
Facilitate research to promote the use of alternative fertilizers, reduce heavy
metals in soil, develop rice strains which require less fertilizer/resistant to pests,
reduce environmental pollution
Ministry of Agriculture - Response
Parliamentary Advisory
Committee on Agriculture
Minimize usage of Agrochemicals
Avoidance of misuse, overuse
& abuse of chemical inputs in
Agriculture
Identification of research needs
by National Committee on Post
Harvest Technology & Human
Nutrition of the Sri Lanka
Council for Agricultural
Research Policy (SLCARP)
15 Recommendations
Submitted as a cabinet paper
Updated Fertilizer
Recommendations for paddy
Banned importation of 4
pesticides
Carbaryl, Chloropyrifos,
Carbofuran, Propanil
Ministry of Agriculture - Cabinet Memorandum
15 Recommendations
1
2
3
4
Establishment of Statutory Technical Council to promote environmentally friendly
agriculture
Establishment of new Sri Lankan Standards (SLS) on pesticides and agrochemicals
To make orders under the Pesticide Control Act to retain heavy metals and
impurities to a minimum possible level
15
Establishing methodology for controlling under-growth
(weeds) of paddy
Re
cultivation & encouraging farmers to cultivate alternate crops for minimizing the
use of pesticide
5
Strengthening legal framework to authorize state officials including the health
sector & Grama niladhari to take legal action against those resorting to
indiscriminate use of pesticides and those supporting the same
6
To prohibit the use of Propane, Glyphosate, Carbayl and Chlorpyrifos
which have been identified as harmful pesticides in areas where kidney diseases
are spreading
Ministry of Agriculture - Cabinet Memorandum (Cont..)
7
In view of the health risk, taking measures to minimize the use of all chemical
fertilizers while encouraging farmers to adopt alternative methods
8
Minimise the use of imported phosphate and increase production and use of
local phosphates
9
Testing all fertilizer varieties with health risk posed due to heavy metal and toxic
ingredient content and establishment of revised standard for the same
10
11
12
Strengthening of legal background & establishment of laboratory facilities for
frequent testing of agro-chemical impurities
Educate the public on the harmful effects on human health due to the use of
agro-chemicals and their safety and efficient use
Prohibit pesticide and agro-chemical fertilliser advertising over electronic & print
media
Ministry of Agriculture - Cabinet Memorandum (Cont..)
13
14
Establishment of a safety method for recycling/disposal of empty pesticide
containers/bottles and fertillizer bags
Providing people in Kidney disease prone areas with drinking water free of
insipid water
15
Impose a 10% health safety cess on all imported pesticide varieties and the levied
amount to be used for welfare of the kidney patients and research activities
Minister (Senior) for Rural Affairs & Chairman of
the Committee to look into the indiscriminate
usage of chemical fertilizer & Agrochemicals
SHORT TERM RECCOMMENDATIONS
1
2
Launch an islandwide program to identify CKDu patients with special attention
to NCP & take action to declare CKDu as a notifiable disease
Carry out surveys using GIS to identify all CKDu hotspots upto Grama Niladhari
Division
3
Declare CKDu hotspots and take all initiatives, to establish casual factors and to
mitigate CKDu in the prevalent areas
4
Establish a high powered policy implementation body to carry out further
research on establishing the exact causal factors of CKDu and to control CKDu
and CKD under an appropriate ministry and to coordinate and implement the
recommendations
Minister (Senior) for Rural Affairs & Chairman of the
Committee to look into the indiscriminate usage of
chemical fertilizer & Agrochemicals (Cont…)
5
Launch a multidisciplinary further research program to cover all spectrum of
CKDu and to strongly establish the causal factor for CKDu
6 Further analyze the fertilizer recommendation scheme while paying specail
attention to the environmental consequence of the scheme
7 Implement an integrated awareness program to address all important aspects of
CKDu and to promote suitable agricultural practices
8
9
Include the impact of heavy metals on human health & environment and safe use
of pesticides and fertilliser into curricular of Geography, Agriculture, Health
Science and science in secondary schools
Establish an independent accredited laboratory & upgrade the existing
laboratories with facilities such as trained staff & sophisticated equipments to
analyse trace elements (Cd, As, Pb,Fe,Mn etc) pesticide residues & other
elements related to CKDu
Minister (Senior) for Rural Affairs & Chairman of the
Committee to look into the indiscriminate usage of
chemical fertilizer & Agrochemicals (Cont…)
10
Regulate the promotional activities related to fertilisers & pesticides carried out
by the agrochemical companies/institutions carried out by mass media
11
Establishment of legal provisions for mandatory requirements in relation to
standards
12
13
14
Provide drinking water with low or no hardness to communities in CKDu
endemic areas by way of providing effective filters and/or delivering portable
water with acceptable quality
Promote & implement rain water harvesting structures with quality monitoring
systems and make regulations for all new buildings in CKDu areas to be
equipped with rain water harvesting units
Select high priority CKDu hotspots & establish “Green Zones” that are free of
major potential CKDu casual inputs
Minister (Senior) for Rural Affairs & Chairman of the
Committee to look into the indiscriminate usage of
chemical fertilizer & Agrochemicals (Cont…)
15
Provide subsidy & marketing facilities for the farmers who make attempts to
move from agrochemicals to alternate farming
16
17
Establish a fund for the welfare of CKDu patients, for carrying out research and
financing for fund through economic instruments based on the polluter pay
principles and producer responsibility as well as CSR
Enhance the medical facilities for CKDu patients with immediate effects in the
affected areas
18
Facilities of the traditional medical practitioners to carry out their treatments for
the affected people based on the patient interest & demand
19
Expedite the establishment of proposed chemical fertilliser manufacturing plant
to produce fertilliser with minimum/standard limits of heavy metals using
Eppawella rock phosphate
Minister (Senior) for Rural Affairs & Chairman of
the Committee to look into the indiscriminate
usage of chemical fertilizer & Agrochemicals
LONG TERM RECCOMMENDATIONS
20
Establish procedures for examination of quality of agrochemicals at boarder poits,
Factory outlets, wholesale & retail shops in the districts
21
Establish long term water quality monitoring system by an accredited agency
under direct supervision of a government institution.
22
Capacity building of grass root level officers to educate farmers on use of
minimum pesticides and fertillisers
23
Prepare necessary maps indicating zones for active, potential and prone to
agrochemical contamination
24
Redesign land use pattern, crop & land implementation plans covering soil &
water drainage engineering aspect & climatic parameters
Minister (Senior) for Rural Affairs & Chairman of the
Committee to look into the indiscriminate usage of
chemical fertilizer & Agrochemicals (Cont…)
25
Establish river banks, green manure banks, neem avenues, herbal gardens,
compost bays and strict declaration of non toxic zones
26
27
28
29
Identify farmers/farmer groups and designate them as responsible agents/agri
environment guard with authority to regulate the inputs used in agriculture
Introduce programmes for organic and sustainable certification to receive
premium prices for farm products
Establish appropriate CSR avenues through Banks, Insurance companies, NGOs,
local institutions for possible subsidy or incentives for proposed curative and
corrective measures
Conduct extended cost benefit analysis for the use of agrochemicals in
consideration of their impact on environmental & social effects
Ministry of Water Supply and Drainage
National Water Supply & Drainage Board
1
Parliamentary Sub committee appointed to coordinate mitigation measures
2 Concept paper and action plans have been prepared for supplying safe drinking
water to all affected areas
3
District wise action items/sub projects have been identified
4
Implementation Plans
SHORT TERM:
•Water for drinking and cooking using small RO (Reverse Osmosis) plants
•Rain water harvesting
MEDIUM TERM:
•Medium sized water supplies based on surface water
•Water Supply extensions
LONG TERM:
•Major Integrated Water Supply projets
Ministry of Social Services
Draft Cabinet paper prepared for
1
To adhere to the Ministry of Health-World Health Organization criteria in order
to diagnose the disease
2
To pay monthly assistance of Rs 1500 each for kidney patients who do not
require dialysis (Stated in Grade 2/3)
3
To pay monthly assistance of Rs 3000 each for kidney patients who require
dialysis (Stated in Grade 3/4)
At present a monthly assistance is paid for only a few
patients through Provincial social Services Department
and ranges from Rs 500 - 1000
Follow-up of Recommendations
Ministry of Health
• Strengthening of the Health Services as per the
recommendations (In progress)
Ministry of Agriculture
• Regulations on Indiscriminate use of Fertilizers
/Pesticides (Cabinet Subcommittee -15 priority areas)
Ministry of Water Supply & • Improvement of Water Quality (Already in
place)
Drainage
Ministry of Indigenous
• Regulatory mechanism to be initiated for reduction of
use of Aristolochia (Sapsanda/Sasanda)
Medicine
Ministry of Environment
Ministry of Science &
Technology
Ministry of Social Services
• Contribution towards reduction of causative
factors
• Supported the National Research effort together with WHO
• Continue research in identified areas
• Strengthening the social service component and facilitating
the provision of patient allowance at an earlier stage
CONCLUSION

Sri Lanka has done work in the area of CKDu over many years.
With a coordinated research initiative over a period of 27
months funded by NSF and WHO has yielded evidence to
initiate policy dialogue which has resulted in the highest political
commitment translated into action by different stakeholders
and ministries.
Thank You